American Indian/Alaska Natives (AI/AN) have historically experienced disparate rates of key reproductive health indicators. In addition, many AI tribes, especially in the western U.S., have been disproportionately affected by exposure to environmental contaminants, including but not limited to non-occupational exposures to uranium and other metal wastes such as arsenic resulting from past mining and milling operations and also from drinking water contamination. In addition, poor socioeconomic conditions affecting many tribal communities often lead to increased rates of alcohol abuse and dependence. While AI/AN are greatly underrepresented in the population-based and targeted screening programs, recent studies among AI of the Northern Plains suggest that the prevalence of the Fetal Alcohol Spectrum Disorder might be 10-fold higher than in the general U.S. population (May et al, 2008). The goal of this project is to partner with the Navajo Birth Cohort Study (NBCS; PI: Lewis) to assess a combined effect of prenatal alcohol, uranium, and arsenic exposure on growth and neurocognitive deficits in 600 Navajo children at 1 year of age. The central hypothesis is that alcohol will synergize with uranium and arsenic co-exposures to increase the risk of early growth and neurodevelopmental deficits at one year of age. The project will employ the state-of-the-art methods to confirm both environmental exposures and prenatal alcohol exposure (PAE) and is supported by Dr. Lewis's extensive preliminary data on uranium and arsenic exposure sources in the Navajo Nation and validation of ethanol biomarkers studies conducted by Dr. Bakhireva. Uranium and arsenic exposures will be determined through in- home environmental assessments, extensive surveys for exposure histories, and through biomonitoring confirmation of recent exposures. In addition to maternal self-report, PAE will be confirmed with a battery of one established (fatty acid ethyl ester [FAEE]) and two novel (ethyl glucuronide [EtG] and ethyl sulfate [EtS]) meconium biomarkers. The presence of FAEE in meconium at birth has been previously reported to be predictive of future mental and psychomotor delays in children, and a battery of three biomarkers is expected to improve sensitivity and specificity of the test. The innovation of the proposed work lies in partnering wit the established NBCS, employing a cost-effective strategy by leveraging NBCS resources, and working within an established, decade-long, community and academic partnership. The proposed study is, to our knowledge, the first attempt to objectively assess prevalence of prenatal alcohol exposure (PAE) and interaction between PAE and environmental toxicants in a Native American population. Both exposures represent potentially modifiable risk factors which might be the key players contributing to health disparities and poor perinatal outcomes in the Native American communities. If the hypothesis is supported by the study outcomes, the findings would have impact beyond the current population.